42 results about "DKK1" patented technology

Provided herein is a method for gene expression profiling multiple myeloma patients into distinct subgroups via DNA hybridization and hierarchical clustering analysis of the hybridization data where the results may further be used to identify therapeutic gene targets. Also provided is a method for controlling bone loss in an individual via pharmacological inhibitors of DKK1 protein. In addition provided herein is a method for diagnosing multiple myeloma using a 15-gene model that classifies myeloma into groups 1-7.

Provided herein are methods for diagnosing and treating multiple myeloma based on statistical analysis of and subsequent increasing / inhibiting expression of subgroups of plasma cells and B cell genes. Also provided are methods for a developmental stage-based classification for multiple myeloma using hierarchical clustering analysis of plasma cell and B cell nucleic acids and for discriminating among normal, hyperplastic and malignant using gene expression array data and statistical analysis thereof. In addition methods for determining the risk of developing bone disease in a test individual by examining expression levels of a WNT signaling antagonist, such as DKK1, are provided. A kit comprising anti-DKK1 antibodies and detection reagents for measuring DKK1 protein levels also is provided.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3 / FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to block bone disease.

Gene expression profiling reveals four distinct subgroups of multiple myeloma that have significant correlation with various clinical characteristics. Diagnosis for multiple myeloma (and possibly monoclonal gammopathy of undetermined significance) based on differential expression of 14 genes, as well as prognosis for the four subgroups of multiple myeloma based on the expression of 24 genes are established. A 15-gene model that classifies myeloma into 7 groups is also reported. Gene expression profiling also allows placing multiple myeloma into a developmental schema parallel to that of normal plasma cell differentiation. Development of a gene expression- or developmental stage-based classification system for multiple myeloma would lead to rational design of more accurate and sensitive diagnostics, prognostics and tumor-specific therapies for multiple myeloma.

The present invention provides antibodies and immunologically functional fragments thereof that specifically bind DKK1 polypeptides. Methods for preparing such antibodies or fragments thereof as well as physiologically acceptable compositions containing the antibodies or fragments are also provided. Use of the antibodies and fragments to treat various diseases are also disclosed.

The invention relates to the technical field of genetic engineering and biomedicine, in particular to an antigen peptide composition and application thereof. The provided antigen peptide composition comprises four antigen peptides, namely the antigen peptide STEAP1, the antigen peptide PSM, the antigen peptide DKK1 and the antigen peptide CD133. The experimental results show that when the antigen peptide composition is adopted, dendritic cell maturation can be effectively induced, the antigen presentation ability is improved, specific cytotoxicity killer cells can be generated, the tumor killing efficiency is improved, the growth of tumors can be effectively inhibited, an anti-tumor effect is achieved, and a new selection is provided for the clinic treatment of the prostatic cancer.

Described herein are antibodies and antibody fragments capable of treating or preventing cancers associated with the over-expression and / or up-regulation of DKK1. Also disclosed are methods of treating or preventing cancer using the antibody and methods and kits utilized to diagnosing cancer. The herein described products and methods find utility in the context of a variety of cancers, such as pancreatic cancer, gastric cancer, liver cancer, prostate cancer, breast cancer, cervical cancer, bile duct cancer, lung cancer and esophageal cancer.

The invention provides methods and compositions for modulating the Wnt signaling pathway, in particular by interfering with binding of Dkk1 or SOST with LRP5 and / or LRP6.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3 / FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to reduce tumor burden in multiple myeloma and to block bone disease.

The finding that Dickkopf1 (Dkk1) is a dual function protein demonstrates a mechanism for the coordination of cell migration and antagonism of Wnt / β-catenin signaling during developmental and pathological processes. The profile of Dkk proteins expressed by human breast cancers correlates with indicators of outcome: Dkk1 associates with markers of poor prognosis whereas expression of single function Dkk2 or Dkk3 (which inhibit Wnt / β-catenin signaling and promote migration, respectively) correlates with phenotypes reflective of good prognosis. Therefore, the pro-migratory activities of Dkk1 and 3 identified here offer new insights into breast cancer progression and a potential avenue for therapeutic intervention.

The present invention relates to a method of culturing primitive-like macrophages from stem cells, a kit when used in the method thereof and uses of the primitive like macrophage for in-vitro disease models and for screening compounds for therapy. One embodied culture method comprises contacting and incubating embryonic stem cells or induced pluripotent stem cells with a serum-free culture media comprising a GSK3 inhibitor to differentiate stem cells into cells of the mesoderm lineage, followed by incubation with a culture media comprising Dickkopf-related protein 1 (DKK1) to differentiate the mesoderm into cells of hematopoietic lineage, maturing hematopoietic cells and incubating these cells with a culture media comprising M-CSF to drive differentiation into primitive-like macrophages. Another embodiment comprises incubating the stem cells with serum-free culture media comprising FGF2 and BMP4 to induce differentiation into cells of the mesoderm lineage, followed by incubating the cells with a culture media comprising FGF2, BMP4, Activin A and VEGF to differentiate the cells of the mesoderm lineage into cells of the hematopoietic cell lineage, maturing the cells of the hematopoietic cell lineage and lastly, incubating the matured hematopoietic cells with culture media comprising M-CSF to drive the differentiation of hematopoietic cells into primitive-like macrophages.

The invention discloses a kit for juvenile osteoporosis detection. Through gene comparison, the fact that compared with a DKK1 gene in the normal people group, a juvenile form osteoporosis patient has the obvious mutant site is discovered, and the obvious mutant site is the 721 site. Through detecting the mutant site, particularly through the pair of provided specific primer pair, whether the people has the juvenile form osteoporosis symptom or not can be specifically identified. Compared with the prior art, the detection method has the advantages that the detection is convenient; accuracy and high speed are realized; the kit is suitable for being popularized and used.

The invention discloses a kit for detecting juvenile osteoporosis. According to the kit, an obvious mutant site which is a site 1020 is discovered to exist in a DKK1 gene in a patient suffering from the juvenile osteoporosis and a normal crowd through genetic comparison. Through detecting the mutant site, particularly provided one pair of specific primer pairs, a human body which suffers from the juvenile osteoporosis can be specifically identified. Compared with the method in the prior art, a detection method has the advantages of being quick for detection, accurate and quick, and is suitable to popularize and use.

The invention discloses an application of a reagent for detecting the expression quantity of immunity related genes, a reagent kit and a head and neck cancer prognosis risk predicting device, and relates to the field of biomedicine. According to the application of the reagent for detecting the expression quantity of the immunity related genes to head and neck cancer prognosis risk disclosed by theinvention, the immunity related genes are selected from the following genes of: RFXAP, ULBP1, TMSB4Y, RBP4, LCNL1, CCR6, KLRK1, PTX3, MASP1, HRG, CCL22, OLR1, ROBO1, BTC, CHGB, DKK1, HBEGF, INHBB, PDGFA, AVPR2, IL20RA, RORB, TNFRSF18, TNFRSF25, TNFRSF4, SH3BP2 and ICOS; according to the expression quantity data of the immunity related genes, the head and neck cancer prognosis risk is predicted; and the reagent has good specificity and good sensitivity.

The present invention provides antibodies and immunologically functional fragments thereof that specifically bind DKK1 polypeptides. Methods for preparing such antibodies or fragments thereof as well as physiologically acceptable compositions containing the antibodies or fragments are also provided. Use of the antibodies and fragments to treat various diseases are also disclosed.